Abstract
Cardiovascular disease is the major cause of death among patients with end stage renal disease and accounts for about half the deaths among the dialysis population. Several researchers have reported a high prevalence of coronary artery disease among diabetic patients with renal failure and coronary arteriography is often considered an integral part of the pretransplant evaluation of diabetic patients with end stage renal disease. However, very few reports have addressed the question of coronary disease in non-diabetic patients, and the pattern and prevalence of coronary artery disease in non-diabetic patients with end stage renal disease are not well defined. We evaluated the clinical and coronary angiographic findings in 158 consecutive patients (84 diabetic and 74 non-diabetic) with end stage renal disease. The coronary arteries were divided into 16 segments and each segment was analyzed for the presence of coronary disease, which was defined as the presence of ≥ 50% luminal diameter stenosis. Diabetic patients had more adverse risk factors for coronary artery disease, yet there was no significant difference in the prevalence of coronary artery disease between the diabetic and non-diabetic patients (67% vs. 55%, p = 0.15), or in the number of affected coronary artery segments (2.0 vs. 1.4, p = 0.05). Triple vessel coronary artery disease was however, significantly more common among the diabetic subjects (27% vs. 12%, p = 0.005). Non-diabetic patients with end stage renal disease also have a high prevalence of coronary artery disease and may merit as careful investigation of their coronary status as their diabetic counterparts.
INTRODUCTION
The cardiac mortality among patients with end stage renal disease (ESRD) is reported to be between 5–20 times higher than the normal population Citation[1-4]. Documented coronary artery disease (CAD) occurs in 20–50% of patients with ESRD and among diabetic patients above the age of 45 years, the prevalence of CAD may be as high as 85% Citation[5-6].
Despite this high burden of CAD among patients with ESRD, there is surprisingly little data on the overall prevalence and pattern of CAD in these patients. Several investigators have utilized noninvasive tests and clinical events as a surrogate marker of CAD. However, factors such as anemia, volume overload, hypertension, electrolyte shifts during dialysis, poor effort tolerance, myopathy, baseline electrocardiographic abnormalities, and pericarditis which are common in patients with ESRD, often conspire to limit the usefulness of non-invasive strategies for the diagnosis of coronary disease. Not surprisingly, the clinical diagnosis of coronary disease in patients with ESRD is often difficult and inaccurate. Even among patients with symptoms and signs of angina pectoris or myocardial infarction with typical electrocardiographic changes, only 53% had angiographically significant coronary artery disease Citation[[7]]. Conversely, in a series of diabetic patients with ESRD, angina symptoms were absent in 75% of patients with angiographically documented coronary artery disease Citation[[8]]. Coronary arteriography therefore continues to be the only method to reliably exclude or diagnose CAD.
Many centers perform coronary arteriography routinely in diabetic patients with ESRD prior to kidney transplantation Citation[[9]]. The American Society of Transplant Physicians (ASTP) also endorses this view and recommends coronary arteriography prior to renal transplantation even in asymptomatic individuals with diabetes Citation[[10]]. However, the available angiographic data does not appear to justify this discrimination between diabetic and non-diabetic patients. In an angiographic study of 58 dialysis patients, diabetes was not found to be associated with CAD Citation[[7]]. Similarly, Joki et al found no difference in the prevalence of angiographically diagnosed CAD among individuals with ESRD due to diabetic and non-diabetic nephropathy Citation[[6]].
While the diabetic patient with ESRD has been the subject of study by several investigators, very few angiographic studies have examined non-diabetic patients or compared diabetic and non-diabetic patients with ESRD. It is therefore possible that CAD is under-diagnosed in many non-diabetic patients with ESRD.
OBJECTIVES
This study was carried out to assess whether non-diabetic patients with ESRD differ from their diabetic counterparts with respect to the prevalence, pattern and severity of coronary artery disease.
METHODOLOGY
We studied 158 consecutive patients with ESRD undergoing coronary arteriography at the Chest Diseases Hospital. There were 84 diabetic and 74 non-diabetic patients. Only patients who were already on a maintenance dialysis program or were being considered for kidney transplant were included. Coronary arteriography was indicated either because of angina chest pain and a clinical suspicion of coronary disease or as part of a routine pre-transplant evaluation. The coronary arteriographic findings in these two groups were compared.
A staff cardiologist to obtain data regarding renal status, dialysis history, angina chest pain, past myocardial infarction, smoking habits and presence of diabetes mellitus and hypertension, interviewed all patients.
The Body Mass Index (weight in Kilograms/square of the height in meters) was used as an index of obesity. Patients were classified as diabetics or hypertensives based on a previous diagnosis by a physician, irrespective of whether they were on treatment or not. Patients who were current smokers or had discontinued smoking in the past ten years were classified as smokers. Hypercholesterolemia was diagnosed if the fasting serum cholesterol level was ≥ 5.2 mmol/L or if they were on lipid lowering therapy. Patient with a history of ischemic heart disease in a first-degree male relative before the age of 55 years or 65 years in a female relative were considered to have a family history of premature ischemic heart disease.
Selective coronary arteriography and left ventriculography were performed using non-ionic contrast media in all patients. Each coronary artery was studied in multiple views to assess the presence and severity of CAD. Two cardiologists, both with experience in coronary interventions independently reviewed all coronary arteriographic films. Stenosis severity was calculated using hand held calipers. Left ventricular end diastolic and end systolic volumes and the ejection fraction were calculated using the Siemens Ancor software (Siemens-Elema AB, Sweden) based on Chapman's modification of Simpson's rule.
Coronary artery disease was defined as the presence of 50% or greater luminal diameter stenosis in any of the three major coronary artery systems. The coronary tree was divided into 16 segments and presence of coronary artery disease in each segment was noted.
CAD confined to any one of the three major epicardial coronary artery systems, (i.e. the left anterior descending coronary artery and its major branches, the left circumflex coronary artery and its major branches, and the right coronary artery and its major branches) was defined as single vessel CAD. Two vessel CAD was defined as significant stenosis in two of the three major coronary artery systems and three vessel CAD defined as significant stenosis in all three major coronary arteries.
Statistical analysis: Mean and standard deviation were calculated for continuous variables, which were then compared using the Student's t-test. The chi square test was used to test the difference between dichotomous variables. A value of p < 0.05 was considered statistically significant.
RESULTS
One hundred and fifty eight consecutive patients with ESRD underwent angiographic evaluation for coronary artery disease. There were 84 diabetic and 74 non-diabetic patients. The mean age of the diabetic patients was 56.1 ± 14.2 years and that of the non-diabetic patients was 53.9 ± 9.5 years (p = ns) (). Diabetics were more likely to have sustained a previous myocardial infarction (19% vs 5%, p = 0.01) or have a family history of premature coronary disease (15% vs 3%, p = 0.006) than non-diabetics. Hypercholesterolemia was diagnosed more commonly among the diabetic than the non-diabetic patients (55% vs. 33%, p = 0.02). Diabetic subjects had a greater body mass index but this difference fell short of statistical significance (26.6 vs. 25.0, p = 0.06). There was no significant difference in the prevalence of the other major risk factors for CAD.
Table 1. Baseline Characteristics
Even though the two groups did not differ in the prevalence of hypertension () or the level of blood pressure measured at the time of cardiac catheterization, (), electrocardiographic evidence of left ventricular hypertrophy was less common among the diabetic patients than the non-diabetic patients (30% vs. 50%, p = 0.009). However, hypertension was present for a shorter duration among the diabetic patients compared to the non-diabetic patients (mean 6.7 vs. 9.3 years, p = 0.024). Abnormal Q waves on the electrocardiogram were more common among the diabetic patients (14% vs. 1%, p = 0.003) ().
Table 2. Ventriculographic and Coronary Angiographic Characteristics
The prevalence of significant coronary disease was not significantly different in the two groups (67% vs. 55%, p = 0.15) (). However, triple vessel CAD was significantly more common among diabetic patients (27% vs. 12%, p = 0.02). Normal coronary arteries were found in 33% of the diabetic patients versus 45% of the non-diabetic patients (p = 0.14). Involvement of the left anterior descending, circumflex and right coronary arteries was equally common among the diabetic and non-diabetic subjects. Similarly, the mean left ventricular ejection fraction and left ventricular volumetric indices did not differ in the two groups.
We also evaluated the number of coronary artery segments with significant coronary artery disease. Involvement of three or more coronary artery segments was more common among diabetic than non-diabetic patients (39% vs. 19%, p = 0.005) (). The mean number of stenosed coronary segments was 2.0 in diabetics and 1.4 in non-diabetic patients, a difference, which was of borderline significance (p = 0.05).
Figure 1. Stenosed coronary segments in diabetic and non-diabetic patients with ESRD.
DISCUSSION
Coronary artery disease is a major determinant of prognosis among patients with renal failure. A high prevalence of CAD has been demonstrated even prior to the onset of dialysis Citation[[6]]. In addition, there is a disturbing propensity for progression of atherosclerosis in patients with ESRD Citation[[11]]. Furthermore, the presence of one or more significant coronary stenoses detected at a pre-transplant evaluation has been shown to increase the risk of subsequent myocardial infarction sevenfold to tenfold Citation[[12]]. The diagnosis of CAD in these patients is thus of considerable importance, especially among prospective renal transplant recipients. Despite this, there is a surprising dearth of information on the basic issue of the pattern and severity of coronary artery disease among patients with ESRD. Most of the available data comes from studies involving relatively small number of patients. To the best of our knowledge, ours is the largest published angiographic study to include both diabetic and non-diabetic patients with ESRD.
The prevalence of diabetes varies widely in different geographical areas. In our hospital, the prevalence of diabetes among patients undergoing coronary angioplasty was reported to be twice as high as the rates reported in the western literature Citation[[13]]. This is also reflected in the high prevalence of diabetic patients in our group with ESRD.
In our study, diabetic patients were more likely to have adverse coronary risk factors such as hyperlipidemia, a family history of premature ischemic heart disease or a history of a previous myocardial infarction. In addition, diabetes itself is a well-recognized risk factor for the development of coronary artery disease as well as kidney failure. Despite this, the overall prevalence of CAD was not significantly greater in the diabetic than the non-diabetic patients. However, coronary disease was more extensive among the diabetic individuals as judged by the involvement of multiple coronary segments and the presence of triple vessel CAD.
Despite the fact that hypertension was equally common among both the groups, left ventricular hypertrophy on the resting electrocardiogram was found more commonly among the non-diabetic patients. This may be explained by the fact that hypertension was more long standing among the non-diabetic group, and may have contributed to the development of renal failure.
We considered the possibility of a referral bias for angiography, to explain the high prevalence of CAD among the non-diabetic patients. However, a comparison of the baseline characteristics revealed more adverse coronary risk factors among the diabetic rather than the non-diabetic subjects. It is therefore unlikely that such a bias contributed to the high prevalence of CAD among the non-diabetic subjects. As our hospital is the only one in the country with facilities for coronary angiography, we were in a position to collect the angiographic data for all patients requiring angiographic evaluation of their coronary status. Our findings are in accord with those of Rostand et al who failed to find an association between diabetes and angiographically diagnosed CAD among dialysis patients Citation[[7]].
We divided our patients based on the presence or absence of diabetes mellitus rather than on the etiology of renal failure. Other investigators have grouped patients as diabetic or non-diabetic nephropathy and yet found no difference in the angiographic prevalence of CAD Citation[[6]]. Since the decision to investigate further often depends on the presence of diabetes, we chose to group all diabetic patients together, irrespective of whether it was considered to be the cause of the renal failure.
Limitations: The majority of our patients were studied as part of a pre-transplant evaluation. Therefore, our findings may not be applicable to all patients with end stage renal disease.
Although non-diabetic individuals had the same overall prevalence of CAD, the severity of the disease was less than their diabetic counterparts. We have not evaluated the prognostic or functional significance of this finding, or its correlation with the various non-invasive tests for myocardial ischemia.
CONCLUSION
Although previous myocardial infarction, hypercholesterolemia and a family history of coronary disease were more common in diabetic patients with ESRD, there was no significant difference in the overall prevalence of coronary disease between the diabetic and non-diabetic groups. Triple vessel CAD was, however, more common among the diabetic patients. Involvement of three or more coronary segments was seen more commonly in diabetic patients with ESRD.
Coronary arteriography may be warranted prior to kidney transplantation even in non-diabetic patients with ESRD.
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